The effect of dietary lactose on the ileal absorption of sodium taurocholate in rats]

When Rats were fed a lactose containing diet, both the absorption rate of sodium taurocholate at the level of ileum and the contents of bile acids of the small intestine were increased. On the contrary, feeding of lactose did not modify the daily fecal excretion of bile acids. It therefore appears that dietary lactose increases the intestinal pool of bile acids by increasing their ileal absorption rate and that this effect of lactose is not subordinated to a modification of bile acid synthesis.     

The functional RNA domain 5BSL3.2 within the NS5B coding sequence influences hepatitis C virus IRES-mediated translation

Hepatitis C virus (HCV) translation is mediated by an internal ribosome entry site (IRES) located at the 5′ end of the genomic RNA. The 3′ untranslatable region (3′UTR) stimulates translation by the recruitment of protein factors that simultaneously bind to the 5′ end of the viral genome. This leads to the formation of a macromolecular complex with a closed loop conformation, similar to that described for the cap-translated mRNAs. We previously demonstrated the existence of a long-range RNA–RNA interaction involving subdomain IIId of the IRES region and the stem–loop 5BSL3.2 of the CRE element at the 3′ end of the viral genome. The present study provides evidence that the enhancement of HCV IRES-dependent translation mediated by the 3′UTR is negatively controlled by the CRE region in the human hepatoma cell lines Huh-7 and Hep-G2 in a time-dependent manner. Domain 5BSL3.2 is the major partner in this process. Mutations in this motif lead to an increase in IRES activity by up to eightfold. These data support the existence of a functional high order structure in the HCV genome that involves two evolutionarily conserved RNA elements, domain IIId in the IRES and stem–loop 5BSL3.2 in the CRE region. This interaction could have a role in the circularisation of the viral genome.     

The life cycle of neutral lipids: synthesis, storage and degradation

Triacylglycerols (TAGs), steryl esters (SEs) and wax esters (WEs) form the group of neutral lipids. Whereas TAGs are present in all types of cell, the occurrence of SEs in prokaryotes is questionable, and the presence of WEs as storage molecules is restricted to plants and a few bacteria. Here, we summarize recent knowledge on the formation, storage and degradation of TAGs and SEs in various cell types. We describe the biochemical pathways involved in TAG and SE synthesis and discuss the subcellular compartmentation of these processes. Recently, several novel enzymes governing the metabolism of storage lipids have been identified and characterized. Regulatory aspects of neutral lipid storage are just beginning to be understood. Finally, we describe consequences of defects in neutral lipid metabolism. Since severe diseases like atherosclerosis, obesity and type 2 diabetes are caused by lipid accumulation, mechanisms underlying neutral lipid synthesis, depot formation and mobilization are of major interest for curing such diseases that are increasingly associated with modern civilization. Received 18 January 2006; received after revision 7 March 2006; accepted 16 March 2006     

The role of myosin phosphorylation in the contraction-relaxation cycle of smooth muscle

Summary Considerable evidence from a variety of experimental procedures indicates that the phosphorylation of myosin is involved in the regulation of contractile activity in smooth muscle. Phosphorylation of the 20,000-dalton myosin light chains is required to initiate crossbridge cycling and this is consistent with the observation that the actin-activated Mg²⁺-ATPase activity of myosin is phosphorylation-dependent. In the simplest interpretation of this process it may be proposed that phosphorylation acts as an on-off switch. Clearly this cannot explain the observed complexity of smooth muscle contractile behavior and such may imply either that additional mechanisms are involved or that the role of myosin phosphorylation is not fully appreciated. Recently it has been shown that monomeric smooth muscle myosin can exist in a folded and an extended conformation and that each form is characterized by distinct enzymatic properties. Under appropriate solvent conditions phosphorylation of myosin favors the extended conformation. It is tentatively suggest that this, or an analogous, transition might be involved in the regulation of the smooth muscle contractile apparatus, and this possibility is discussed.The authors are supported by grants HL 23615 and HL 20984 from the National Institutes of Health.     

The variation of adenosine triphosphate and adenosine triphosphatase inTribolium confusum,duval at the different stages of its life cycle

Résumé Un homogénat brut deTribolium confusum Duval peut hydrolyser les molécules d'ATP, d'ADP, d'AMP et d'-glycérophosphate. L'activité de l'ATPase dépend des ions Mg⁺⁺ et Ca⁺⁺. La courbe illustrant les variations de l'activité de cette ATPase en fonction du pH, montre deux pH optima, l'un à 7.5 et l'autre à 8.5. L'activité de l'ATPase est élevée durant la période larvaire, alors que la croissance est active et elle est faible durant la période pupale. La concentration de l'ATP est toujours inversement proportionnelle à l'activité de l'ATPase et cela à tous les stades du cycle vital de l'insecte.

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This work was supported by a grant (A-1388) received from the National Research Council of Canada.     

The metabolism, pharmacokinetics and mechanisms of antiviral activity of ribavirin against hepatitis C virus

Ribavirin, a broad spectrum antiviral agent, in conjunction with interferon forms the current standard of treatment for hepatitis C virus (HCV) infection in humans. While ribavirin alone fails to induce a significant antiviral response, in combination with interferon, ribavirin dramatically improves the long-term outcome of therapy. The predominant mechanism(s) of ribavirin action against HCV, are yet to be established. In this review, we examine the current status of our understanding of the metabolism, pharmacokinetics and mechanisms of the antiviral activity of ribavirin against HCV, all of which are central to the rational identification of improved treatment protocols. Received 30 September 2005; received after revision 20 November 2005; accepted 7 December 2005     

Composition and functional role of the mucus layers in the intestine

In discussions on intestinal protection, the protective capacity of mucus has not been very much considered. The progress in the last years in understanding the molecular nature of mucins, the main building blocks of mucus, has, however, changed this. The intestinal enterocytes have their apical surfaces covered by transmembrane mucins and the whole intestinal surface is further covered by mucus, built around the gel-forming mucin MUC2. The mucus of the small intestine has only one layer, whereas the large intestine has a two-layered mucus where the inner, attached layer has a protective function for the intestine, as it is impermeable to the luminal bacteria.     

Titers of ecdysone, 20-hydroxyecdysone and juvenile hormone III throughout the life cycle of a hemimetabolous insect,the ovoviviparous cockroachNauphoeta cinerea

Summary Titers of ecdysone, 20-hydroxyecdysone and juvenile hormone III were measured in whole body extracts or hemolymph of embryos, first, penultimate and last stadium nymphs, and adult females ofNaupoheta cinerea. We used a gas-chromatography/mass spectrometry method for quantifying juvenile hormone and a radio-immunoassay for ecdysteroid determination. Juvenile hormone III is particularly abundant in the embryonic stage (up to 960 ng/g), at a low level in first and penultimate stadium nymphs (2–10 ng/ml) and almost absent in the last nymphal stadium; in the adult female the juvenile hormone titer rises to 180 ng/ml in hemolymph during rapid oocyte growth. The titers of ecdysone and 20-hydroxyecdysone undergo similar fluctuations in the embryonic and nymphal stages, being highest at the time of cuticle formation in the embryo and a few days before the nymphal and adult molts (around 100–200 ng/ml for exdysone and 2–4 g/ml for 20-hydroxyecdysone).Acknowledgments. We thank Mrs A. Tschan for rearing the cockroaches, Mr M. Kaltenrieder for drawing the graphs, Mr G.C. Jamieson and Mrs C. Reuter for GC/MS analyses. We are also grateful to the Swiss National Science Foundation (grant no. 3.291-0.82 to B. Lanzrein) and the United States National Science Foundation (grant no. PCM 82-08665 to D.A. Schooley) for their financial support.     

Molecular mimicry and the role of B lymphocytes in the processing of autoantigens

The immune system has evolved several mechanisms that provide lymphocytes with the intelligence to ignore self proteins while attacking foreign pathogenic agents. Notably, B and T lymphocytes that encounter self antigen at either the inappropriate levels or affinity are usually instructed to perish or become anergized. However, the presence of autoimmune disease suggests that the induction of self tolerance is not foolproof. In fact, autoreactive cells are now found to be normal inhabitants of the B and T lymphocyte repertoire. This review examines how foreign peptides which resemble self proteins can elicit autoimmunity that is amplified to many sites on a target autoantigen. In particular, B lymphocytes initiated by foreign molecular mimics can process and present self peptides in the shaping of autoimmune T cell responses.